Dr. Page is an associate professor of clinical pharmacy and physical medicine at the University of Colorado, Denver, Schools of Pharmacy and Medicine.
Stroke has been defined as a "heterogeneous, neurologic syndrome characterized by gradual or rapid, nonconvulsive onset of neurologic deficits that fit a known vascular territory and that lasts for 24 hours or more."1 In other words, this disease can be characterized as a sudden impairment of normal body functioning caused by a disruption in the supply of blood to a specific area in the brain. This impairment may be transient, lasting several days or even permanently. In the United States, an individual experiences a stroke every 45 seconds. This statistic equates to approximately 700,000 Americans annually. About 500,000 of these are first-time or primary strokes, while the remaining are recurrent or secondary strokes. Each year, stroke claims approximately 155,000 lives, making it the third leading killer in the United States behind cardiovascular disease and cancer.2
Appropriate Candidates for Alteplase
- Diagnosis of ischemic stroke causing measurable neurologic deficit
- Neurologic signs should not be clearing spontaneously
- Neurologic signs should not be minor and isolated
- Caution should be exercised in treating a patient with major deficits
- Symptoms of stroke should not be suggestive of subarachnoid hemorrhage
- Onset of symptoms <3 hours before beginning treatment
- No head trauma or prior stroke in previous 3 months
- No myocardial infarction in previous 3 months
- No gastrointestinal or urinary tract hemorrhage in previous 21 days
- No major surgery in previous 14 days
- No arterial puncture at a noncompressible site in previous 7 days
- No history of previous intracranial hemorrhage
- BP not elevated (systolic <185 mm Hg and diastolic <110 mm Hg)
- No evidence of active bleeding or acute trauma (fracture) on examination
- Not taking an oral anticoagulant or, if anticoagulant being taken, INR <1.7
- If receiving heparin in previous 48 hours, aPTT must be in normal range
- Platelet count ≥100,000 mm3
- Blood glucose concentration ≥50 mg/dL (2.7 mmol/L)
- No seizure with postictal residual neurologic impairments
- CT scan does not show a multilobar infarction (hypodensity ≥1/3 cerebral hemisphere)
- The patient or family members understand the potential risks and benefits from treatment
Review of Stroke Pathophysiology
Stroke can be classified into 2 types: (1) ischemic, which is caused by a blood clot within the brain, accounting for 75% to 80% of all strokes, and (2) hemorrhagic, which occurs when weakened cerebral arteries rupture, leading to subarachnoid or intracerebral bleeding.2 Ischemic stroke is caused by emboli, thrombus, or systemic hypoperfusion. Forty-five percent of ischemic strokes are due to embolic causes, which may be due to atrial fibrillation, patent foramen ovale, and low ejection fraction. Thrombus accounts for 30% of ischemic stroke and is associated with plaque buildup and atherosclerosis. The remaining 25% can be attributed to systemic hypoperfusion, hypercoagulable states, and cryptogenic etiologies.2
The signs and symptoms most commonly reported by patients suffering from an acute stroke are unilateral paralysis or weakness; difficulty with speech, gait, or coordination; and the "worst" headache of the patient's life.3 Other symptoms include facial droop, altered vision, sensory impairment, or thought process interference.4,5
ABCs for Acute Ischemic Stroke
As pharmacists, we have all been taught the "ABCs" of basic life support, (airway, breathing, and circulation). While these definitely apply to the emergent management of stroke, a more drug-focused set of ABCs are more specific for the pharmacist. Once in the emergency department, the focus of management should be to determine if indeed the patient is having a stroke, treating the stroke with alteplase (a tissue plasminogen activator), when applicable—the "A" in the ABCs—and identifying other conditions warranting immediate intervention. Table 1 summarizes appropriate candidates for alteplase therapy. Guidelines for administering alteplase are listed in Table 2. Blood pressure (BP), the "B" in our ABCs, plays a crucial role in ischemic stroke, as it can be a cause and/or complication poststroke. High BP can affect the patient outcome and also may delay alteplase administration. An excessively high BP also can contribute to hemorrhagic transformation following alteplase administration. Current guidelines recommend treating a systolic BP >220 mm Hg or a diastolic BP >120 mm Hg.6 Finally, the "C" in our mnemonic is controlling the patient's blood glucose concentrations (BGCs). In the heat of the moment, practitioners may forget to closely monitor the BGC; however, an elevated BGC needs to be recognized and treated immediately. Evidence indicates that persistent hyperglycemia (>140 mg/dL) during the first 24 hours poststroke is associated with poor clinical outcomes. Whereas this concentration may not seem elevated, recent stroke guidelines recommend that the BGC be maintained in the range of 80 to 140 mg/dL and that the use of insulin be initiated in these cases.6
By remembering and using these 3 simple ABCs, pharmacists within any health system can play a significant role in the emergent management of a patient with an acute ischemic stroke.
Administration of IV Alteplase
- Infuse 0.9 mg/kg (maximum dose 90 mg) over 60 minutes, with 10% of the dose given as a bolus over 1 minute
- Admit the patient to an intensive care or stroke unit for monitoring
- Perform neurologic assessments every 15 minutes during the infusion and every 30 minutes thereafter for the next 6 hours, then hourly until 24 hours after treatment
- If the patient develops severe headache, acute hypertension, nausea, or vomiting, discontinue the infusion (if alteplase is being administered) and obtain emergency CT scan
- Measure BP every 15 minutes for the first 2 hours and subsequently every 30 minutes for the next 6 hours, then hourly until 24 hours after treatment
- Increase the frequency of BP measurements if a systolic BP is ≥180 mm Hg or if a diastolic BP is ≥105 mm Hg; administer antihypertensive medications to maintain BP at or below these levels
- Delay placement of nasogastric tubes, indwelling bladder catheters, or intra-arterial pressure catheters
- Obtain a follow-up CT scan at 24 h before starting anticoagulants or antiplatelet agents
IV = intravenous; BP = blood pressure; INR = international normalized ratio; aPTT = activated partial thromboplastin time; CT = computed tomography.
Adapted from reference 6.
- Hickey JV, Hock NH. Stroke and other cerebrovascular diseases. In: Hickey JV, ed. Clinical Practice of neurological and neurosurgical nursing. Philadelphia, PA: Lippincott, Williams & Wilkins; 2003.
- Heart Disease and Stroke 2008 Update At-a-Glance Statistics. American Heart Association Web site. www.americanheart.org/downloadable/heart/1200078608862HS_Stats%202008.final.pdf. Accessed July 3, 2008.
- Suwanwela N, Koroshetz WJ. Acute ischemic stroke: overview of recent therapeutic developments. Annu Rev Med. 2007;58:89-106.
- Rathore SS, Hinn AR, Cooper LS, Tyroler HA, Rosamond WD. Characterization of incident stroke signs and symptoms: findings from the atherosclerosis risk in communities study. Stroke. 2002;33:2718-2721.
- Toole JF, Lefkowitz DS, Chambless LE, Wijnberg L, Paton CC, Heiss G. Self-reported transient ischemic attack and stroke symptoms: methods and baseline prevalence. The ARIC Study, 1987-1989. Am J Epidemiol. 1996;144:849-856.
- Adams HP Jr, del Zoppo G, Alberts MJ, et al. Guidelines for the early management of adults with ischemic stroke: a guideline from the American Heart Association/American Stroke Association Stroke Council, Clinical Cardiology Council, Cardiovascular Radiology and Intervention Council, and the Atherosclerotic Peripheral Vascular Disease and Quality of Care Outcomes in Research Interdisciplinary Working Groups: the American Academy of Neurology affirms the value of this guideline as an educational tool for neurologists. Stroke. 2007;38(5):1655-1711.